A program project applying a polyvalent approach directed toward the elucidation of the physiological roles of neural peptides in regulating the endocrine and central nevous systems (CNS). Three hypothalamic peptides have been isolated and characterized to date based on their pituitary actions. These are TRF, LRF and somatostatin (SS). We are involved in the isolation and biological and chemical characterization of several unidentified putative factors modifying pituitary function. In addition, we are investigating various aspects of the biochemistry, physiology and pathophysiology of the characterized peptides TRF, LRF and SS including their: (1) mechanisms of biosynthesis and secretion, (2) conformation, (3) structure/functions in normal subjects, (5) possible roles in pathological situations. In addition, we are designing and testing analogs of these peptides which would have possible therapeutic applications to human problems such as fertility control, endocrine cancer, diabetes mellitus and behavioral disorders. Physiology of the secretion of endorphins as it relates to that of ACTH is also currently explored. Separation of multiple components from highly purified insulin is explored by high resolution chromatography; studies of metabolic and mitogenic activities of these components other than "true" insulin is contemplated.